EMD-39159

Subtomogram averaging
6.2 Å
EMD-39159 Deposition: 18/02/2024
Map released: 19/06/2024
Last modified: 18/09/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-39159

SARS-CoV-2 DMV nsp3-4 pore complex (full-length-pore)

EMD-39159

Subtomogram averaging
6.2 Å
EMD-39159 Deposition: 18/02/2024
Map released: 19/06/2024
Last modified: 18/09/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 nsp3-4 pore complex

Deposition Authors: Huang YX , Zhong LJ, Zhang WX, Ni T
Molecular architecture of coronavirus double-membrane vesicle pore complex.
Huang Y, Wang T, Zhong L , Zhang W, Zhang Y, Yu X , Yuan S , Ni T
(2024) Nature , 633 , 224 - 231
PUBMED: 39143215
DOI: doi:10.1038/s41586-024-07817-y
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
Coronaviruses remodel the intracellular host membranes during replication, forming double-membrane vesicles (DMVs) to accommodate viral RNA synthesis and modifications1,2. SARS-CoV-2 non-structural protein 3 (nsp3) and nsp4 are the minimal viral components required to induce DMV formation and to form a double-membrane-spanning pore, essential for the transport of newly synthesized viral RNAs3-5. The mechanism of DMV pore complex formation remains unknown. Here we describe the molecular architecture of the SARS-CoV-2 nsp3-nsp4 pore complex, as resolved by cryogenic electron tomography and subtomogram averaging in isolated DMVs. The structures uncover an unexpected stoichiometry and topology of the nsp3-nsp4 pore complex comprising 12 copies each of nsp3 and nsp4, organized in 4 concentric stacking hexamer rings, mimicking a miniature nuclear pore complex. The transmembrane domains are interdigitated to create a high local curvature at the double-membrane junction, coupling double-membrane reorganization with pore formation. The ectodomains form extensive contacts in a pseudo-12-fold symmetry, belting the pore complex from the intermembrane space. A central positively charged ring of arginine residues coordinates the putative RNA translocation, essential for virus replication. Our work establishes a framework for understanding DMV pore formation and RNA translocation, providing a structural basis for the development of new antiviral strategies to combat coronavirus infection.